Supplementation of diets with α-tocopherol reduces serum concentrations of γ- and δ-tocopherol in humans

Despite promising evidence from in vitro experiments and observational studies, supplementation of diets with α-tocopherol has not reduced the risk of cardiovascular disease and cancer in most large-scale clinical trials. One plausible explanation is that the potential health benefits of α-tocopherol supplements are offset by deleterious changes in the bioavailability and/or bioactivity of other nutrients. We studied the effects of supplementing diets with RRR-α-tocopheryl acetate (400 IU/d) on serum concentrations of γ- and δ-tocopherol in a randomized, placebo-controlled trial in 184 adult nonsmokers. Outcomes were changes in serum concentrations of γ- and δ-tocopherol from baseline to the end of the 2-mo experimental period. Compared with placebo, supplementation with α-tocopherol reduced serum γ-tocopherol concentrations by a median change of 58% [95% CI = (51%, 66%), P < 0.0001], and reduced the number of individuals with detectable δ-tocopherol concentrations (P < 0.0001). Consistent with trial results were the results from baseline cross-sectional analyses, in which prior vitamin E supplement users had significantly lower serum γ-tocopherol than non-users. In view of the potential benefits of γ- and δ-tocopherol, the efficacy of α-tocopherol supplementation may be reduced due to decreases in serum γ- and δ-tocopherol levels. Additional research is clearly warranted.